Elucidating the origin of microglia is crucial for understanding their functions and homeostasis. Previous study has indicated that Nestin-positive progenitor cells differentiate into microglia and replenish the brain after depleting most brain microglia. Microglia have also shown the capacity to repopulate the retina after eliminating all retinal microglia. However, the origin(s) of repopulated retinal microglia is/are unknown. In this study, we aim to investigate the origins of repopulated microglia in the retina. Interestingly, we find that repopulated retinal microglia are not derived from Nestin-positive progenitor cells. Instead, they have two origins: the center-emerging microglia are derived from residual microglia in the optic nerve and the periphery-emerging microglia are derived from macrophages in the ciliary body/iris. Therefore, we have for the first time identified the extra-retinal origins of microglia in the adult mammalian retina by using a model of microglial repopulation, which may shed light on the target exploration of therapeutic interventions for retinal degenerative disorders.

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The methanogenic degradation of oil hydrocarbons can proceed through syntrophic partnerships of hydrocarbon-degrading bacteria and methanogenic archaea [1][2][3] . However, recent culture-independent studies have suggested that the archaeon 'Candidatus Methanoliparum' alone can combine the degradation of long-chain alkanes with methanogenesis 4,5 . Here we cultured Ca. Methanoliparum from a subsurface oil reservoir. Molecular analyses revealed that Ca. Methanoliparum contains and overexpresses genes encoding alkyl-coenzyme M reductases and methyl-coenzyme M reductases, the marker genes for archaeal multicarbon alkane and methane metabolism. Incubation experiments with different substrates and mass spectrometric detection of coenzyme-M-bound intermediates confirm that Ca. Methanoliparum thrives not only on a variety of long-chain alkanes, but also on n-alkylcyclohexanes and n-alkylbenzenes with long n-alkyl (C ≥13 ) moieties. By contrast, short-chain alkanes (such as ethane to octane) or aromatics with short alkyl chains (C ≤12 ) were not consumed. The wide distribution of Ca. Methanoliparum 4-6 in oil-rich environments indicates that this alkylotrophic methanogen may have a crucial role in the transformation of hydrocarbons into methane.In subsurface oil reservoirs and marine oil seep sediments, microorganisms use hydrocarbons as a source of energy and carbon 7,8 . The microorganisms preferentially consume alkanes, cyclic and aromatic compounds, leaving an unresolved complex mixture as residue and thereby altering the quality of the oil 7,8 . In the absence of sulfate, microorganisms couple anaerobic hydrocarbon degradation to methane formation 1,9,10 . This reaction was originally demonstrated by Zengler et al 2 as methanogenic 'microbial alkane cracking', and a large number of studies have shown that it can be performed in syntrophic interactions of bacteria and archaea 11 . In this syntrophy, the bacteria ferment the oil to acetate, carbon dioxide and hydrogen, while hydrogenotrophic and/or acetotrophic methanogenic archaea use the products for methanogenesis 1,2,11 .Diverse anaerobic hydrocarbon activation mechanisms exist, including the well-studied fumarate addition pathway catalysed by glycyl radical enzymes 12 . This mechanism is widespread among bacteria that thrive on alkanes of various chain lengths and other hydrocarbons 12,13 . By contrast, several archaeal lineages activate gaseous alkanes with the help of a specific type of methyl-coenzyme M reductase (MCR), an enzyme that was originally described to catalyse the reduction of methyl-coenzyme M (methyl-CoM) to methane in methanogens 14 . Anaerobic methanotrophic archaea use canonical MCRs to activate methane into methyl-CoM, which is then oxidized to CO 2 . Short-chain alkane-oxidizing archaea contain divergent variants of this enzyme, which are known as alkyl-CoM reductases (ACRs). Analogous to the methane-activating MCR, ACRs activate multicarbon alkanes to form CoM-bound alkyl units [15][16][17] . The cultured alkane-oxidizing archaea oxidize sho...